Experiments concerned with the molecular aspects of circadian rhythms are directed towards an ultimate understanding of both the mechanism and the nature of the physiological control exerted by these systems. Two unicellular forms, the dinoflagellate Gonyaulax and the alga Chlamydomonas are being studied, including a new investigation of the effects of newly available inhibitors. Since Chlamydomonas has a well defined phototactic rhythm, and its genetic system has already been described, it is being used to select and analyze rhythm mutants, especially with regard to the biochemical nature of lesions associated with specific phenotypes. Up to now there are no clearly defined biochemical correlates of rhythmicity in this cell; these studies may provide new information along these lines. With Gonyaulax on the other hand we do have a well defined biochemical correlate of the in vivo rhythm of bioluminescence: the luciferase activity in extracts varies with time of day in concert with the rhythm. As the first step in obtaining an understanding of the control mechanism we are exploring the nature of this activity change-- whether by synthesis and destruction or by a cycle of activation and inhibition. The results indicate the latter, but the precise molecular mechanism has not yet been established. The situation is complicated by the fact that luciferase occurs in an array of molecular sizes, whose interrelationship and functional importance is under investigation. Ultrastructural aspects of the luminescence system are also being investigated.